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Objectives: To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women., Methods: Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine., Results: Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less., Conclusion: Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.

Objective: To review biomedical determinants of women's vulnerability to infection with HIV and interventions to counter this, within the southern African context., Results: Apart from number of exposures, if any, several factors influence the efficiency of HIV transmission during sex. Acute HIV infection, with extraordinarily high semen viral load, in conjunction with concurrent partnerships maximizes this efficiency. Delaying sexual debut and avoiding HIV exposure among biologically and socially vulnerable youth is critical. Reducing unintended pregnancies keeps girls in school and prevents vertical (also possibly horizontal) transmission. Female condoms, especially newer versions, are an under-exploited prevention technology. Control of sexually transmitted infections (STI), which facilitate HIV acquisition and transmission, remains important, especially among the most at-risk populations. Pathogens, such as herpes simplex virus type 2, which contribute most to HIV transmission in southern Africa must be targeted, although the importance of bacterial vaginosis and Trichomonas vaginalis is under-recognized. Also, heavy episodic alcohol use affects sexual decision-making and condom skills. Moreover, prevailing social contexts, partly a consequence of poor leadership, constrain the behavioural 'choices' available for girls and women., Conclusions: Priority health sector interventions for preventing HIV are: male and female condom programming; prevention and control of STI; outreach to most vulnerable populations; HIV testing in all patient-provider encounters; male circumcision; and the integration of HIV prevention within sexual and reproductive health services. Future interventions during acute HIV infection and microbicides will reduce women's biological vulnerability. Far-reaching measures, such as sexual equity and alcohol control, create conditions necessary for achieving sustained prevention results. These are, however, contingent on stronger, more informed cultural and political leadership.

Background: Young women in sub-Saharan Africa are at very high risk of HIV acquisition, and high prevalence levels have been observed among women reporting one lifetime partner and few sexual contacts. Such findings have led to hypotheses that the probability of HIV transmission from men to women must be far higher than previously appreciated., Methods: We used the data from a cross-sectional national household survey of HIV among South African women aged 15-24 years to estimate the per-partnership transmission probability from men to women. Estimates were obtained using maximum likelihood methods and a transmission probability model allowing for random error in the self-reported number of lifetime partners. Sensitivity analyses were employed to assess the robustness of the per-partnership transmission probability estimates to the assumed HIV prevalence in male partners., Results: HIV prevalence in women was 21.2% (95% confidence interval 17.9-24.5). The mean reported number of lifetime partners was 2.3. A significant increase in prevalence was observed with increasing lifetime partner numbers (P = 0.02). For a range of plausible values of the partner prevalence, the estimated per-partnership transmission probability varied from 0.74 to 1.00 with 95% confidence intervals ranging from 0.56 to 1.00., Discussion: The per-partnership probability of HIV transmission from men to women in this population was very high. Before this, the majority of studies examining per-partnership transmission probabilities estimated values below 50%. Identifying the factors that may drive the efficient spread of HIV in sub-Saharan Africa is essential for the development of effective prevention interventions.

Objectives: To determine the prevalence of HIV infection, HIV risk factors, and exposure to national HIV prevention programs, and to identify factors associated with HIV infection among South African youth, aged 15-24 years., Design: A cross-sectional, nationally representative, household survey., Methods: From March to August 2003 we conducted a national survey of HIV prevalence and sexual behavior among 11 904 15-24 year olds. Multivariable models for HIV infection were restricted to sexually experienced youth., Results: Young women were significantly more likely to be infected with HIV in comparison with young men (15.5 versus 4.8%). Among men, a history of genital ulcers in the past 12 months was associated with HIV infection [adjusted odds ratio (AOR), 1.91; 95% confidence interval (CI), 1.04-3.49) whereas among women a history of unusual vaginal discharge in the past 12 months was associated with HIV infection (AOR, 1.75; 95% CI, 1.26-2.44). Young women with older partners were also at increased risk of HIV infection. Among both men and women, increasing partner numbers and inconsistent condom use were significantly associated with HIV infection. Males and females who reported participation in at least one loveLife program were less likely to be infected with HIV (AOR, 0.60; 95% CI, 0.40-0.89; AOR, 0.61; 95% CI, 0.43-0.85, respectively)., Conclusion: This survey confirms the high HIV prevalence among young people in South Africa and, in particular, young women's disproportionate risk. Programs for youth must continue to promote partner reduction, consistent condom use and prompt treatment for sexually transmitted infections while also addressing contextual factors that make it difficult for them to implement behavior change.